Effects of the antioxidants dihydrolipoic acid (DHLA) and probucol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in vitro

• Published in: Environmental toxicology and pharmacology Vol. 9; no. 4; pp. 161 - 167
• Main Authors: Coleman, Michael D., Baker, Claire D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2001
• Subjects: Antioxidants; Diabetic and non-diabetic human erythrocytes; Dihydrolipoic acid; Methaemoglobin formation; p-Aminophenol; Probucol; Xenobiotic; Antioxidants; Diabetic and non-diabetic human erythrocytes; Probucol; Methaemoglobin formation; Dihydrolipoic acid; Xenobiotic
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/S1382-6689(01)00061-8

The antioxidant effects of dihydrolipoic acid (DHLA) and probucol were investigated in a human erythrocytic in-vitro model of diabetic oxidative stress, where xenobiotics were used to form methaemoglobin. 4-Aminophenol mediated haemoglobin oxidation in non-diabetic erythrocytes was not affected by the presence of either DHLA or probucol. However, with diabetic cells, there were significant increases (
P<0.01) in 4-aminophenol-mediated haemoglobin oxidation in the presence of DHLA. Methaemoglobin formed by nitrite in non-diabetic and diabetic cells was not altered by either DHLA or probucol except at one time point in diabetic cells. In non-diabetic as well as diabetic cells, methaemoglobin formed by MADDS-NHOH was significantly reduced at all three time points in the presence of DHLA (
P<0.0001) but unaffected by probucol. In the presence of DHLA only, methaemoglobin formed by the products of rat microsomal oxidation of both 4-aminopropiophenone and benzocaine was markedly reduced for both xenobiotics in diabetic and non-diabetic cells (
P<0.0001) compared with cells incubated in the absence of DHLA. There were no significant differences between total cellular thiol levels determined between diabetic and non-diabetic erythrocytes, nor did DHLA or probucol affect resting thiol levels. MADDS-NHOH caused a significant thiol depletion in diabetic cells, which was restored in the presence of DHLA. A further study is required to determine how DHLA attenuates the potent REDOX reactions that occur during hydroxylamine-mediated methaemoglobin formation.